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The metabolomic differences between the peels of Citrus reticulata ‘Chachi’ and different varieties of Citrus unshiu Marc. were analyzed to provide a theoretical basis and scientific evidence for the development and utilization of the peels of Citrus unshiu Marc.. The chemical composition of Citrus reticulata ‘Chachi’ (CZG) and three different varieties of Citrus unshiu Marc. (‘Youliang’ (YL), ‘Nangan 20’ (NG) and ‘Gongchuan’ (GC)) were determined by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and the metabolomic data were comparatively analyzed using principal component analysis (PCA), orthogonal partial least square-discriminant analysis (OPLS-DA) and cluster analysis (CA) to screen differential metabolites. Through database comparison, 790, 796 and 818 metabolites were identified between CZG and YL, NG and GC, respectively, with organic oxides, flavonoids, carboxylic acids and their derivatives accounting for the highest proportions, which are mainly involved in the metabolic pathways of flavonoid and flavanol biosynthesis, isoflavones biosynthesis, α-linolenic acid metabolism, and phenylpropanoid biosynthesis. Using the cutoff of variable importance in the projection (VIP) score > 1 with P value < 0.05, stable and reliable differential metabolites were selected. A total of 43 differential metabolites of 11 classes were identified between Citrus reticulata ‘Chachi’ and Citrus unshiu Marc., the predominant ones being flavonoids, amino acids and purine nucleosides. Most flavonoids in Citrus unshiu Marc. such as 5, 6, 7, 8, 3’, 4’, 5’-heptamethoxyflavone, quercetin, naringenin, and naringenin were up-regulated, which could be used as potential markers to differentiate Citrus reticulata ‘Chachi’ from Citrus unshiu Marc.. Furthermore, Citrus unshiu Marc. had a higher content of flavonoids and therefore could be used as a source of Citri Reticulatae Pericarpium.

Previous studies have shown that some anesthesia drugs can inhibit tumor growth and metastasis. As a clinical anesthetic drug, dezocine has been reported to play an important role in immune function. However, the effects of dezocine on ovarian cancer cell growth and metastasis are not fully understood. In this study, we found that dezocine dose-dependently inhibited the viability of ES-2 and SKOV3 cells. Dezocine suppressed the migration and invasion abilities of ovarian cancer cells, and promoted apoptosis. Moreover, the Akt/mTOR signaling pathway was also inhibited by dezocine. Furthermore, mechanism study showed that dezocine could significantly inhibit the expression of CRABP2, and CRABP2 overexpression reversed the inhibitory effects of dezocine on ovarian cancer cell proliferation and migration. In conclusion, dezocine has significant anti-tumor effects on the growth and metastatic potential of ovarian cancer cells, and CRABP2 functions as a downstream effector of dezocine.

INTRODUCTION: More robust non‐human primate models of Alzheimer's disease (AD) will provide new opportunities to better understand the pathogenesis and progression of AD. METHODS: We designed a CRISPR/Cas9 system to achieve precise genomic deletion of exon 9 in cynomolgus monkeys using two guide RNAs targeting the 3′ and 5′ intron sequences of PSEN1 exon 9. We performed biochemical, transcriptome, proteome, and biomarker analyses to characterize the cellular and molecular dysregulations of this non‐human primate model. RESULTS: We observed early changes of AD‐related pathological proteins (cerebrospinal fluid Aβ42 and phosphorylated tau) in PSEN1 mutant (ie, PSEN1‐ΔE9) monkeys. Blood transcriptome and proteome profiling revealed early changes in inflammatory and immune molecules in juvenile PSEN1‐ΔE9 cynomolgus monkeys. DISCUSSION: PSEN1 mutant cynomolgus monkeys recapitulate AD‐related pathological protein changes, and reveal early alterations in blood immune signaling. Thus, this model might mimic AD‐associated pathogenesis and has potential utility for developing early diagnostic and therapeutic interventions. Highlights: A dual‐guide CRISPR/Cas9 system successfully mimics AD PSEN1‐ΔE9 mutation by genomic excision of exon 9.PSEN1 mutant cynomolgus monkey‐derived fibroblasts exhibit disrupted PSEN1 endoproteolysis and increased Aβ secretion.Blood transcriptome and proteome profiling implicate early inflammatory and immune molecular dysregulation in juvenile PSEN1 mutant cynomolgus monkeys.Cerebrospinal fluid from juvenile PSEN1 mutant monkeys recapitulates early changes of AD‐related pathological proteins (increased Aβ42 and phosphorylated tau). [ABSTRACT FROM AUTHOR]

Background and Hypothesis This study investigated the role of the medial prefrontal cortex (mPFC)-basolateral amygdala (BLA) pathway in schizophrenia (SCZ)-related cognitive impairments using various techniques. Study Design This study utilized clinical scales, magnetic resonance imaging, single-cell RNA sequencing, and optogenetics to investigate the mPFC-BLA pathway in SCZ patients. In the mouse model, 6-week-old methylazoxymethanol acetate-induced mice demonstrated significant cognitive deficits, which were addressed through stereotaxic injections of an adeno-associated viral vector to unveil the neural connection between the mPFC and BLA. Study Results Significant disparities in brain volume and neural activity, particularly in the dorsolateral prefrontal cortex (DLPFC) and BLA regions, were found between SCZ patients and healthy controls. Additionally, we observed correlations indicating that reduced volumes of the DLPFC and BLA were associated with lower cognitive function scores. Activation of the mPFC-BLA pathway notably improved cognitive performance in the SCZ model mice, with the targeting of excitatory or inhibitory neurons alone failing to replicate this effect. Single-cell transcriptomic profiling revealed gene expression differences in excitatory and inhibitory neurons in the BLA of SCZ model mice. Notably, genes differentially expressed in the BLA of these model mice were also found in the blood exosomes of SCZ patients. Conclusions Our research provides a comprehensive understanding of the role of the PFC-BLA pathway in SCZ, underscoring its significance in cognitive impairment and offering novel diagnostic and therapeutic avenues. Additionally, our research highlights the potential of blood exosomal mRNAs as noninvasive biomarkers for SCZ diagnosis, underscoring the clinical feasibility and utility of this method. [ABSTRACT FROM AUTHOR]

Background: Inflammation and dysregulated immunity play vital roles in idiopathic pulmonary arterial hypertension (IPAH), while the mechanisms that initiate and promote these processes are unclear. Methods: Transcriptomic data of lung tissues from IPAH patients and controls were obtained from the Gene Expression Omnibus database. Weighted gene co-expression network analysis (WGCNA), differential expression analysis, protein-protein interaction (PPI) and functional enrichment analysis were combined with a hemodynamically-related histopathological score to identify inflammation-associated hub genes in IPAH. The monocrotaline-induced rat model of pulmonary hypertension was utilized to confirm the expression pattern of these hub genes. Single-cell RNA-sequencing (scRNA-seq) data were used to identify the hub gene-expressing cell types and their intercellular interactions. Results: Through an extensive bioinformatics analysis, CXCL9, CCL5, GZMA and GZMK were identified as hub genes that distinguished IPAH patients from controls. Among these genes, pulmonary expression levels of Cxcl9, Ccl5 and Gzma were elevated in monocrotaline-exposed rats. Further investigation revealed that only CCL5 and GZMA were highly expressed in T and NK cells, where CCL5 mediated T and NK cell interaction with endothelial cells, smooth muscle cells, and fibroblasts through multiple receptors. Conclusions: Our study identified a new inflammatory pathway in IPAH, where T and NK cells drove heightened inflammation predominantly via the upregulation of CCL5, providing groundwork for the development of targeted therapeutics. [ABSTRACT FROM AUTHOR]